Exploring Heading Direction Perception in Cervical Dystonia, Tremor, and Their Coexistence.

OBJECTIVE: Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one's own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. We compare such perception behavior in visual and vestibular domains, predicting that visual heading perception would be superior to vestibular heading perception. METHODS: Following the focus on the perception of heading direction, we used psychophysics techniques, such as two-alternative-forced-choice task, to examine perception of direction of one's own movements as they see isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). We fitted a sigmoidal psychometric function curve to determine the threshold for visual or vestibular heading perception in our participants. RESULTS: Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions-isolated cervical dystonia, isolated tremor, and their combination. CONCLUSION: These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing.

Unraveling the Twist: Spatial Navigational Challenges in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is an intricate neurological condition with motor and nonmotor symptoms. These include disruptions in visual perception, self-orientation, visual working memory, and vestibular functions. However, the specific impact of CD on perceiving self-motion direction, especially with isolated visual or vestibular stimuli, remains largely unexplored. OBJECTIVE: This study aimed to examine the effects of CD on linear motion perception, hypothesizing impaired heading discrimination in both vestibular and visual tasks, and that such deficits correlate with the disease severity. METHODS: We employed a cutting-edge motion platform to precisely control whole-body linear motion. Through repeated two-alternative forced-choice tasks, we assessed vestibular heading direction discrimination. Participants observed dynamic star clouds in immersive virtual reality and indicated their perceived self-motion direction, evaluating visual heading direction discrimination. Sensitivity to direction variations and response accuracy errors were analyzed using robust Gaussian cumulative distribution psychometric functions. RESULTS: Heading perception is impaired in individuals with CD, particularly evident in vestibular heading discrimination. CD severity correlated with elevated thresholds for both vestibular and visual heading discrimination. Surprisingly, lateralized CD did not introduce bias in either system, suggesting widespread disruption over localized effects. CONCLUSIONS: Contrary to previous beliefs, our findings challenge the idea that CD-related heading discrimination issues mainly arise from peripheral vestibular effects. Instead, abnormal proprioceptive input from dystonic neck muscles introduces noise into the central mechanism integrating visual, vestibular, and proprioceptive signals. These insights into spatial navigation deficits have implications for future CD research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Establishment of glycosaminoglycan assays for mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs.